Schistosoma mansoni is one of the world's most common infectious organisms. It continues to afflict poor people, especially children, in much of the developing world and most prominently in tropical Africa. We propose a series of studies to investigate the potential impact of several relevant selective factors on the biology of this parasite, both in its molluscan and human hosts. The proposed studies will be done in collaboration with Dr. Gerald M. Mkoji of the Kenya Medical Research Institute (KEMRI) and will take place in Kisumu, Kenya, near Lake Victoria. Our efforts will interface with those of an ongoing KEMRI project undertaken in collaboration with the Center for Disease Control and Prevention (CDCP), headed by Dr. Diana Karanja of the Kisumu KEMRI office and Dr. Evan Secor of the CDCP. The KEMRI-CDCP study has enrolled -300 human subjects in a long-term study exploring the immunobiology of S. mansoni, including its interactions with HIV-I. Largely from the same pool of human subjects we will obtain miracidia from fecal samples and develop methods for assessing the genetic diversity among miracidia as a means to make inferences about the adult worm populations harbored by humans. We also will adapt new assays to detect praziquantel (PZQ) susceptibility of both miracidia and cercariae. With these tools, we will determine if and how concurrent HIV infection or PZQ exposure, including repeated exposure, alter the genetic composition of S. mansoni, or favor the emergence of PZQ resistance. We will also look for signs of genetic introgression of a sympatric and closely related parasite, Schistosoma rodhaini, that we know hybridizes with S. mansoni in the Lake Victoria area. We will examine naturally infected snails to learn if they emit cercariae at unusual times of the day as a practical indicator of hybridization, and determine if multiple parasite genotypes are present within individual snails. Cercariae from these snails will also be tested for their responsiveness to PZQ. Finally we will undertake experimental snail infections to better understand how schistosome infections are acquired by snails in Kisumu, and to learn if S. mansoni and S. rodhaini either compete or cooperate to achieve infections in the snail host. Our studies will develop new epidemiological tools, create unique synergies with the KEMRI-CDCP project and will enable us to better understand how S. mansoni will respond to the vast environmental changes underway in Africa today.